The principal objective of this project is to study the intraneuronal twisted tubules which are the morphological hallmark of human senile and presenile dementia. We expect to isolate the twisted tubules and characterize them with respect to molecular weight, peptide mapping, and amino acid composition. These findings will be used to compare the twisted tubules with normally-occurring neuro-tubules and neurofilaments. We will also study the age-dependent synthesis and turnover of microtubule and filament proteins. Attempts will be made to isolate 100 A filaments from cells with aluminum- induced neurofibrillary proliferation, and to compare these filaments to normally-occurring filaments and tubules. Using atomic absorption method, aluminum content will be determined in isolated twisted tubules, neurofilaments, and tubulin. Antitubulin antibodies and their reaction to twisted tubules and filaments will also be studied. The methods of procedure outlined in this grant proposal include biochemical and immunological methodology, light and electron microscopic studies. The senile and presenile dementias are one of the greatest financial burdens on society today. This research offers the possibility of opening fruitful studies of the biochemical defects in the affected neurons.